Out of many esters, various esters of guanidinobenzoic acid are known to be useful as medicines, for example, useful in the treatment of acute pancreatitis etc. owing to their anti-plasmin activity and anti-trypsin acitivity and in the treatment of pulmonary emphysema etc. owing to their inhibitory activity on elastase.
Recently, as a result of their detailed research on pharmacokinetics in oral administration of the above esters, the present inventors have found unexpected facts. That is, it has been confirmed that these esters are degraded by the action of various esterase in digestive system, especially in intestine comparatively rapidly.
Esters of guanidinobenzoic acid are degraded to guanidino benzoic acid and an alcohol corresponding to the ester moiety (when a medicine has plural ester-bonds, it is presumed that the bonds is severed in order of facility in breaking and finally the medicine is degraded to guanidinobenzoic acid and another part. Any degradation products have no desired pharmacological effect or have the structure not to be absorbed, and therefore, the bioavailability of the esters of guanidinobenzoic acid descends.
Furthermore, it has turned out that other esters and amides which are considered to be degraded by the action of various esterases and peptidases in digestive system, are degraded comparatively rapidly, similarly to esters of guanidinobenzoic acid.
As a result of their energetic investigation in order to find means to inhibit the degradation of the esters or amides by the action of digestive enzymes (e.g. various esterases and peptidases) in digestive system, the present inventors have found that the purpose is accomplished by suspending or dissolving the said esters or amides in MCGs, and having completed the present invention.
In the specification of the Japanese Patent Kokai No. 55-17328, W/O/W-formed emulsion comprising insulin as active agent and middle chain triglycerides (referred to as "MCT" hereafter) etc. as oily substance, and inhibiting the degradation by the action of digestive enzymes, is disclosed. In the composition, MCT is used as oily substance which the oily phase in W/O/W-formed emulsion is composed of. At the point, there is fundamental difference in structure from the MCG suspensions or solutions of the present invention, and further, such W/O/W-formed emulsion does not suggest the present invention at all.
Furthermore, no other prior arts relating to MCGs suspensions or solutions for inhibiting the degradation of active ingredients by the action of digestive enzymes, have been known. Further, no compositions comprising suspensions or solutions of guanidinobenzoic acid derivatives in MCGs have so far been known.